This project involves the refinement and validation of a new instrument for the evaluation of vascular endothelial function. This instrument, the "Vascular Relaxoscope," is able to measure the relaxation of the arterial wall in response to increased flow with 37% greater sensitivity than existing non-invasive methods. The relaxoscope can be manufactured for under $5,000, and its operation does not require significant operator experience (between-observer variability in novice operators is less than 3%). The relaxoscope operates by inducing artificial blood pressure pulses at the superficial radial artery. These pulses are detected at a proximal location along the artery using an ultrasound (US) sensor. In this way, pulse transit time (PTT) can be measured. Since PTT is related to the tone of the smooth muscle in the arterial wall, stimulus-induced change in PTT constitutes a most sensitive physical measure of the integrity of vasorelaxatory response. Other methods that quantify vasorelaxation via diameter increase are necessarily less sensitive, since diameter change is but one of several consequences of smooth muscle relaxation. Impairment of the endothelial function is a primary early event in atherosclerosis arid correlates strongly with the major risk factors for cardiovascular (CV) disease. It is also an extremely sensitive and specific predictor of the CV events that constitute the single largest cause of death in the Western world. The most widely used non-invasive measure of endothelial function involves the measurement of brachial artery diameter using US imaging before and after several minutes of arm blood flow occlusion. The change in arterial diameter is a measure of flow-mediated vasorelaxation. However, the high variability of results and high equipment cost render this technique unsuitable for routine use. The relaxoscope is designed to fill this clinical role. The objectives of this project are (1) to demonstrate the ability of the relaxoscope to predict confirmed coronary artery disease in human subjects and (2) to refine the instrument by building custom hardware optimized for the detection of artificially induced blood pressure pulses, improving the ergonomics so that measurements may be more conveniently obtained from a larger range of subjects, investigating pneumatic methods of inducing artificial arterial pulses and their detection using photoplethysmographic techniques, and through studies to determine whether pharmacological agents may be used to stimulate the vascular endothelium instead of occlusive cuff-based methods.